PTAB

IPR2023-00050

TWi Pharmaceuticals Inc v. Merck Serono SA

Title: Cladribine Regimen for Treating Multiple Sclerosis
Brief Description: The ’903 patent describes a method for treating relapsing-remitting or early secondary progressive multiple sclerosis (MS) by orally administering cladribine. The method follows a specific sequence of an induction period, a drug-free period, a maintenance period, and another drug-free period with defined total dosages.

Prior Art Relied Upon: Bodor (Patent 7,888,328).
Core Argument for this Ground:
- Prior Art Mapping: Petitioner argued that Bodor alone discloses every limitation of the challenged claims. Bodor teaches an oral cladribine treatment for MS comprising administration for 5-7 days in a first month and a second month (a two-month induction period), followed by ten months of no treatment (a cladribine-free period). Petitioner contended that Bodor’s disclosed dosage range, when calculated for an average-weight patient, anticipates the claimed induction dosage of about 1.7 mg/kg. The petition asserted that a person of ordinary skill in the art (POSITA) would infer from Bodor and standard clinical practice that this 12-month cycle would be repeated to treat a chronic condition like MS. This inferred second cycle would constitute the claimed maintenance period and subsequent cladribine-free period, with a POSITA applying the same 1.7 mg/kg dosage, which was standard practice for subsequent treatment rounds.
- Key Aspects: The core of this argument relied on a POSITA inferring the repetition of Bodor's treatment cycle to meet the maintenance period limitations, an interpretation Petitioner noted was adopted by the Examiner during the original prosecution.

Prior Art Relied Upon: Bodor (Patent 7,888,328) and the common knowledge of a POSITA.
Core Argument for this Ground:
- Prior Art Mapping: This ground presented an alternative to the anticipation argument. If Bodor was found not to inherently teach the repetition of its treatment cycle, Petitioner argued it would have been obvious for a POSITA to do so. Bodor discloses the initial induction period, dosage, and drug-free period. The common knowledge of a POSITA would supply the understanding that immunotherapies for chronic diseases are administered in multiple rounds.
- Motivation to Combine: A POSITA would be motivated to repeat the treatment cycle taught by Bodor because it was well-known that a single round of immunotherapy was unlikely to be sufficient to effectively treat MS. Standard medical practice for such conditions involved repeated administration phases to manage symptoms over time.
- Expectation of Success: A POSITA would have had a high expectation of success. Clinicians had successfully administered other immunosuppressants for multiple rounds using the same dosage for each round. Therefore, applying this standard, repeated-cycle approach to Bodor's oral cladribine regimen would have been a predictable and effective treatment strategy.

Prior Art Relied Upon: Bodor (Patent 7,888,328) and Rice (a 2000 article in Neurology).
Core Argument for this Ground:
- Prior Art Mapping: This ground provided an explicit evidentiary basis for repeating the treatment cycle if not inferred from Bodor alone or supplied by common knowledge. Bodor teaches the initial oral dosing regimen, while Rice explicitly discloses retreating MS patients with cladribine after a 12-month drug-free period and demonstrates the benefits of doing so.
- Motivation to Combine: A POSITA would combine Bodor's oral regimen with Rice's teaching of retreatment. Rice demonstrated that retreatment led to positive long-term outcomes, such as the virtual elimination of gadolinium-enhancing brain lesions. These promising results would have motivated a POSITA to apply the successful retreatment strategy from Rice to the specific oral formulation and dosing schedule taught by Bodor. Furthermore, Bodor itself cited Rice as a relevant reference for cladribine dosing.
- Expectation of Success: Rice’s reported efficacy and positive trend toward a beneficial effect in long-term follow-up provided a strong expectation that repeating the Bodor regimen would be a successful method for treating MS.

§325(d) - Same Art/Arguments: Petitioner argued denial under §325(d) was improper because, while Bodor was before the Examiner during prosecution, the Examiner made a material error by misapprehending the scope of claim 17. The patent owner successfully distinguished prior art from claim 1 by arguing the art did not teach a maintenance dose lower than the induction dose. However, claim 17 is broader and covers an embodiment where the maintenance dose is equal to the induction dose. Petitioner contended the Examiner overlooked this distinction and never properly examined the patentability of the "equal dose" embodiment, which Petitioner asserts Bodor teaches.
§314(a) - Fintiv Factors: Petitioner argued against discretionary denial under Fintiv, acknowledging a parallel district court case but asserting that all factors weighed against denial. The petition highlighted that the parallel litigation was in its earliest preliminary stages, with no trial date set and minimal investment by the court or parties. Crucially, the Petitioner is not a party to the parallel litigation, a factor that Petitioner argued weighs strongly against exercising discretion to deny institution.

Petitioner requested institution of an inter partes review and a final written decision canceling claims 17, 19-20, and 22-29 of the ’903 patent as unpatentable.